Renal effects of norepinephrine-induced variations in mean arterial pressure after liver transplantation: A randomized cross-over trial.

BACKGROUND: Acute kidney injury is commonly seen after liver transplantation. The optimal perioperative target mean arterial pressure (MAP) for renal filtration, perfusion and oxygenation in liver recipients is not known. The effects of norepinephrine-induced changes in MAP on renal blood flow (RBF), oxygen delivery (RDO2 ), glomerular filtration rate (GFR) and renal oxygenation (=renal oxygen extraction, RO2 Ex) were therefore studied early after liver transplantation. METHODS: Ten patients with an intra- and post-operative vasopressor-dependent systemic vasodilation were studied early after liver transplantation during sedation and mechanical ventilation. To achieve target MAP levels of 60, 75 and 90 mm Hg, the norepinephrine infusion rate was randomly and sequentially titrated. At each target MAP, data on cardiac index (CI), RBF and GFR were obtained by transpulmonary thermodilution (PiCCO), the renal vein thermodilution technique and renal extraction of chromium ethylenediaminetetraaceticacid (51 Cr-EDTA), respectively. Renal oxygen consumption (RVO2 ) and extraction (RO2 Ex) were calculated according to standard formulas. RESULTS: At a target MAP of 75 mm Hg, CI (13%), RBF (18%), RDO2 (24%), GFR (31%) and RVO2 (20%) were higher while RO2 Ex was unchanged compared to a target MAP of 60 mm Hg. Increasing MAP from 75 up to 90 mm Hg increased RVR by 38% but had no further effects on CI, RBF, RDO2 or GFR. CONCLUSIONS: In patients undergoing liver transplantation, RBF and GFR are pressure-dependent at MAP levels below 75 mm Hg. Our results suggest that MAP should probably be targeted to approximately 75 mm Hg for optimal perioperative renal filtration, perfusion and oxygenation in patients undergoing liver transplantation.

Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N-acetyl-ß-D-glucosaminidase.

BACKGROUND: Acute kidney injury (AKI) is a common complication with a major impact on morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB). The aim of the present study was to perform a detailed analysis on the release of the tubular injury biomarker N-acetyl-b-D-glucosaminidase (NAG) during and early after CPB and to describe independent predictors of maximal tubular injury. We hypothesized that renal tubular injury occurs early after the onset of CPB. METHODS: In this prospective observational study, we included 61 patients undergoing open cardiac surgery with an expected CPB duration exceeding 60 min. The urinary NAG levels were measured at 30 min intervals during CPB, as well as early (30 min) after CPB and post-operatively. Independent predictors of tubular injury were identified using an Interquantile multivariate regression model. RESULTS: Already 30 min after the onset of CPB, NAG excretion was significantly increased (P < 0.001), followed by a sixfold peak increase after discontinuation of CPB (P < 0.001). In the multivariable regression model, CPB duration (P < 0.05) and the degree of rewarming during CPB (P < 0.05), were independent predictors of peak NAG excretion. CONCLUSION: In cardiac surgery, a renal tubular cell injury is seen early after onset of CPB with a peak biomarker increase early after end of CPB. The magnitude of this tubular injury is independently related to CPB duration and the degree of rewarming. Efforts made to decrease the CPB duration and to avoid hypothermia and the need for rewarming may decrease the risk for tubular injury.

Effects of acute plasma volume expansion on renal perfusion, filtration, and oxygenation after cardiac surgery: a randomized study on crystalloid vs colloid.

BACKGROUND: In the present randomized study, we evaluated the differential effects of a colloid and a crystalloid fluid on renal oxygen delivery (RD(O2)), glomerular filtration (GFR), renal oxygen consumption ((RV(O2))), and the renal oxygen supply-demand relationship (i.e., renal oxygenation) after cardiac surgery with cardiopulmonary bypass. METHODS: Thirty patients with normal preoperative renal function, undergoing uncomplicated cardiac surgery, were studied in the intensive care unit in the early postoperative period. Patients were randomized to receive a bolus dose of either a crystalloid (Ringers-acetate 20 ml kg(-1), n=15) or a colloid solution (Venofundin) 10 ml kg(-1), n=15). Systemic haemodynamics were measured via a pulmonary artery catheter. Renal blood flow and GFR were measured by the renal vein retrograde thermodilution technique and by renal extraction of 51Cr-EDTA (=filtration fraction). Arterial and renal vein blood samples were obtained for measurements of renal oxygen delivery (RD(O2)) and RV(O2). Renal oxygenation was estimated from the renal oxygen extraction. RESULTS: Despite an increase in cardiac index and renal blood flow with both fluids, neither of the fluids improved RD(O2), because they both induced haemodilution. The GFR increased in the crystalloid (28%) but not in the colloid group. The crystalloid increased the filtration fraction (24%) and renal oxygen extraction (23%), indicating that the increase in GFR, the major determinant of RV(O2), was not matched by a proportional increase in RD(O2). CONCLUSIONS: Neither the colloid nor the crystalloid improved RD(O2) when used for postoperative plasma volume expansion. The crystalloid-induced increase in GFR was associated with impaired renal oxygenation, which was not seen with the colloid. CLINICAL TRIAL REGISTRATION: NCT01729364.

Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patients.

BACKGROUND: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine-dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post-cardiac surgery patients. METHODS: Twelve patients were studied during sedation and mechanical ventilation after cardiac surgery. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h. At each infusion rate, systemic haemodynamics were evaluated by a pulmonary artery catheter, and RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of 51chromium-ethylenediaminetetraacetic acid, respectively. RVO2 and RO2Ex were calculated by arterial and renal vein blood samples. RESULTS: The mean arterial pressure was not affected by vasopressin while cardiac output and heart rate decreased. RBF decreased and GFR, filtration fraction, sodium reabsorption, RVO2, RO2Ex and renal vascular resistance increased dose-dependently with vasopressin. Vasopressin exerted direct antidiuretic and antinatriuretic effects. CONCLUSIONS: Short-term infusion of low to moderate, non-hypertensive doses of vasopressin induced a post-glomerular renal vasoconstriction with a decrease in RBF and an increase in GFR in post-cardiac surgery patients. This was accompanied by an increase in RVO2, as a consequence of the increases in the filtered tubular load of sodium. Finally, vasopressin impaired the renal oxygen demand/supply relationship.

Loss of heterozygosity at chromosome 6q correlates with tumor progression and patient survival.

Several chromosome regions exhibit loss of heterozygosity (LOH) in human breast carcinoma and are thought to carry tumor suppressor genes. We have analysed human breast tumors with 9 polymorphic microsatellite markers that are specific to chromosome 6q. The mapping of smallest region of overlap (SRO) indicated location of candidate suppressor genes at 6q23 and 6q27. Variations in estrogen receptor (ER) expression were independent of the number of copies of the corresponding gene. Tumors with and without LOH on chromosome 6q were tested for association with clinicopathological factors. A significant association was found between LOH at 6q and the following: high S-phase, aneuploidy, deletions at chromosomes 3p and 9p and lower survival rate. In a multivariate model LOH at 6q is an independent prognostic variable and patients having tumors with LOH have approximately twofold increase in relative risk of death. It can be concluded that the 6q deletions give additional prognostic information that might be useful in breast cancer treatment.